J Pharmacol Exp Ther. 1990 Nov;255(2):491-6.
Renal disposition and effects of naproxen and its l-enantiomer in the isolated perfused rat kidney.

Cox PG, Moons WM, Russel FG, van Ginneken CA.

Department of Pharmacology, University of Nijmegen, The Netherlands.

Renal handling, metabolism and effects on kidney function of naproxen and its l-enantiomer were examined in the isolated perfused rat kidney (IPK). Urinary excretion rate of naproxen was much lower than the filtration rate, indicating extensive reabsorption. Naproxen is accumulated considerably in the IPK. This accumulation is concentration-dependent and is probably the result of active secretion of naproxen. Considerable amounts of desmethyl-naproxen were formed in the IPK. The kinetic behavior of the l-enantiomer of naproxen did not differ from naproxen. Addition of 37.5 to 3750 micrograms naproxen caused a decrease in urinary flow, glomerular filtration rate and fractional excretion of sodium, chloride, potassium, magnesium and calcium. The presence of prostaglandin E2 in the perfusate fully opposed the effects of naproxen on kidney function. Addition of 375 micrograms l-enantiomer of naproxen did not influence kidney function. Addition of very high doses (1 x 10(5) micrograms) of naproxen and its l-enantiomer to the IPK caused diuresis and increased the fractional excretion of sodium, chloride, potassium, glucose and calcium. We conclude that the pharmacokinetic behavior and the metabolism of naproxen in the IPK is probably not stereoselective; that relatively low doses of naproxen exert a specific, stereoselective effect on kidney function caused by inhibition of the prostaglandin E2 synthesis and that high doses of naproxen exert a nonstereoselective effect on kidney function.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2243339&dopt=Abstract Naproxen Naprosyn





Semin Arthritis Rheum. 1987 Feb;17(3 Suppl 2):36-9.
Naproxen: antirheumatic efficacy and safety in patients with pre-existing gastrointestinal disease.

Roth SH.

Arthritis Center, Arizona Institutes, Phoenix 85012.

Nonsteroidal antiinflammatory drugs (NSAIDs) effectively reduce pain and inflammation of rheumatoid arthritis (RA). To further refine the appropriate uses of NSAID therapy, NSAIDs have been evaluated for possible gastrotoxicity, particularly in patients who have pre-existing gastrointestinal (GI) disease. In the present study, 58 such RA patients (36 women, 22 men) treated long-term with naproxen were monitored for periods up to 2.5 years to determine if any gastrotoxicity were induced by naproxen. We found an extremely low incidence of fecal occult blood, patient complaints of GI discomfort, complications documented by GI studies, and patient discontinuance of naproxen therapy because of complaints. Studies reported in the medical literature support our observations that naproxen can be well tolerated and is effective as long-term RA treatment when patients who have clinically significant pre-existing GI disease are managed with conventional treatments and appropriate monitoring.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3508328&dopt=Abstract Naproxen Naprosyn





Pharm Res. 1991 Feb;8(2):242-6.
Sulfate homeostasis. III. Effect of chronic naproxen or sulindac treatment on inorganic sulfate disposition in arthritic patients with renal impairment.

Morris ME, Freer JP, Watson WA.

Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.

The purpose of the present investigation was to examine the influence of chronic naproxen (500 mg twice daily) or sulindac (200 mg twice daily) therapy on the disposition of inorganic sulfate in arthritic subjects with impaired renal function. Subjects were studied during a control period (after a 7-day NSAID washout) and after 14 days of treatment with either naproxen or sulindac. During the control period subjects in this investigation exhibited higher serum sulfate concentrations and lower sulfate renal clearance values than reported for younger subjects with normal renal function. Treatment with either sulindac or naproxen significantly decreased creatinine clearance. Sulindac therapy also increased the serum sulfate concentration and decreased the clearance of sulfate; a similar trend was observed after naproxen therapy but the average change was smaller and not statistically significant. There were significant correlations between the creatinine and the sulfate clearances or serum concentrations. The glomerular filtration rate of inorganic sulfate was not altered by drug treatment and there was no impairment of reabsorption. The serum concentrations and renal clearance of other electrolytes (sodium, potassium, magnesium, calcium, phosphorus) were largely unaffected. Therefore, chronic treatment with naproxen or sulindac decreases the renal clearance of endogenous sulfate in humans: this appears to be a consequence of the decrement in renal function observed in subjects with preexisting mild renal impairment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2023875&dopt=Abstract Naproxen Naprosyn





Agents Actions. 1984 Oct;15(3-4):428-35.
Possible disease-modifying effects of naproxen in the adjuvant-arthritic rat.

Ackerman NR, Kappas K, Maloney P.

Naproxen was evaluated for possible disease modifying effects in the Freund's adjuvant injected rat (AIR). Oral administration of the clinical dose, 7 mg/kg/day, lead to an almost complete inhibition of hindpaw swelling and cartilage and bone erosion. This was noted in animals maintained on drug as well as those in which therapy was discontinued. AIR, comparable to arthritic patients, demonstrate a reduced lymphocytic response to T cell mitogens. This response was normalized in naproxen-treated rats. These results suggest that naproxen has a disease modifying effect in the AIR.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6335353&dopt=Abstract Naproxen Naprosyn





Headache. 1993 Apr;33(4):191-4.
Disposition of naproxen after oral administration during and between migraine attacks.

Pini LA, Bertolotti M, Trenti T, Vitale G.

Clinical Pharmacology Department, University of Modena, Italy.

Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Ten patients were treated with 500 mg of a soluble form of naproxen during and between migraine attacks. Clinical parameters and drug plasma levels were recorded at scheduled times. Pain reduction, from severe to mild was evident by 6.5 +/- 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8496057&dopt=Abstract Naproxen Naprosyn





Arzneimittelforschung. 1980;30(5):843-6.
[Serum protein binding and elimination half-lives of naproxen in patients with hepatocellular or obstructive icterus (author's transl)]

[Article in German]

Held H.

Serum protein binding of (+)-6-methoxy-alpha-methyl-2-naphthaline acetic acid (naproxen) is considerably reduced in patients with hepatocellular or obstructive icterus, respectively. There is a significant negative correlation between serum bilirubin concentration and serum protein binding of naproxen. However, bilirubin cannot be responsible exclusively for the reduced naproxen binding. This has been shown by studies with serum to which bilirubin was added in vitro. The hypothetical plasma concentration at the time zero and the half-lives of naproxen were not altered in patients with hepatocellular or obstructive icterus in comparison with healthy subjects. This may possibly cause an increased pharmacologic effect of naproxen in icteric patients when the drug is administered in usual doses. For in this case the pharmacologically active unbound part of the drug must be increased.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7190433&dopt=Abstract Naproxen Naprosyn





J Pharm Sci. 1989 Apr;78(4):324-7.
Effect of R and S enantiomers of naproxen on aggregation and thromboxane production in human platelets.

Kean WF, Lock CJ, Rischke J, Butt R, Buchanan WW, Howard-Lock H.

Department of Medicine Laboratory for Inorganic Medicine, McMaster University, Hamilton, Ontario, Canada.

The effects of R and S enantiomers of naproxen [(+)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid] were studied on platelet aggregation and on the production of thromboxane B2 from collagen-stimulated human platelets in order to determine the effect of each enantiomer in terms of cyclooxygenase inhibition. S-Naproxen caused inhibition of platelet aggregation in platelet-rich plasma and washed human platelets in a concentration-related fashion in the range 1-80 micrograms/L. A similar concentration-related suppression was noted for R-naproxen, but this inhibition was significantly less than that induced by S-naproxen for all concentrations except 1 micrograms/L. Similarly, both R- and S-naproxen (1-80 micrograms/L) caused a concentration-dependent suppression of thromboxane B2 production from platelet-rich plasma. These values were significant at all concentrations of drug (10-80 micrograms/L) except at 1 micrograms/L. Significant differences in thromboxane B2 production from washed human platelets were noted at concentrations of 10 and 25 micrograms/L. The findings support previous studies reported in the literature that S-naproxen is more active than R-naproxen. Our findings that S-naproxen is more active than R-naproxen on collagen-stimulated platelet aggregation and prostaglandin production suggest that the findings of greater activity of S isomer over the R isomer in animal models of inflammation may be a direct expression of the differential action on prostaglandin synthesis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2724096&dopt=Abstract Naproxen Naprosyn